The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation (original) (raw)

1. Charlotte Andrieu-Soler1,7,
2. Ernie de Boer1,7,
3. Jan Christian Bryne2,8,
4. Supat Thongjuea2,8,
5. Ralph Stadhouders1,
6. Robert-Jan Palstra1,
7. Mary Stevens1,
8. Christel Kockx3,
9. Wilfred van IJcken3,
10. Jun Hou1,
11. Christine Steinhoff4,
12. Erikjan Rijkers5,
13. Boris Lenhard2,11 and
14. Frank Grosveld1,6,10
15. 1Department of Cell Biology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands;
16. 2Computational Biology Unit-Bergen Center for Computational Science and Sars Centre for Marine Molecular Biology, University of Bergen, N-5008 Bergen, Norway;
17. 3Biomics Department, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands;
18. 4Department of Computational Biology, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
19. 5Department of Biochemistry, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands;
20. 6Center for Biomedical Genetics and Cancer Genomics Center, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands
21. ↵7 These authors contributed equally to this work.
22. ↵8 These authors contributed equally to this work.

Abstract

One of the complexes formed by the hematopoietic transcription factor Gata1 is a complex with the Ldb1 (LIM domain-binding protein 1) and Tal1 proteins. It is known to be important for the development and differentiation of the erythroid cell lineage and is thought to be implicated in long-range interactions. Here, the dynamics of the composition of the complex—in particular, the binding of the negative regulators Eto2 and Mtgr1—are studied, in the context of their genome-wide targets. This shows that the complex acts almost exclusively as an activator, binding a very specific combination of sequences, with a positioning relative to transcription start site, depending on the type of the core promoter. The activation is accompanied by a net decrease in the relative binding of Eto2 and Mtgr1. A Chromosome Conformation Capture sequencing (3C-seq) assay also shows that the binding of the Ldb1 complex marks genomic interaction sites in vivo. This establishes the Ldb1 complex as a positive regulator of the final steps of erythroid differentiation that acts through the shedding of negative regulators and the active interaction between regulatory sequences.

Keywords:

• ChIP sequencing
• transcription factor complexes
• development
• differentiation
• erythropoiesis
• long-range interactions

Footnotes

• ↵9 Corresponding authors.
  E-MAIL e.soler{at}erasmusmc.nl; FAX 31-10-7044743.

• ↵10 E-MAIL f.grosveld{at}erasmusmc.nl; FAX 31-10-7044743.

• ↵11 Corresponding author for informatics.
  E-MAIL boris.lenhard{at}bccs.uib.no; FAX 47-555-84295.

• Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.551810.

• Supplemental material is available at http://www.genesdev.org.

• Received August 5, 2009.

• Accepted December 4, 2009.

• Copyright © 2010 by Cold Spring Harbor Laboratory Press

Freely available online through the Genes & Development Open Access option.